CHEMISTRY & BIODIVERSITY – Vol. 4 (2007) 721 REVIEW RNA: Prebiotic Product, or Biotic Invention? by Carole Anastasi, Fabien F. Buchet, Michael A. Crowe, Alastair L. Parkes, MatthewW. Powner , James M. Smith, and John D. Sutherland* School of Chemistry, University of Manchester, Oxford Road, Manchester M139PL, UK (phone: ( þ44)1612754614; fax: (þ44)1612754939; e-mail:
[email protected]) Spectacular advances in structural and molecular biology have added support to the RNA world hypothesis, and provide a mandate for chemistry to explain how RNA might have been generated prebiotically on the early earth. Difficulties in achieving a prebiotically plausible synthesis of RNA, however, have led many to ponder the question posed in the title of this paper. Herein, we review recent experimental work on the assembly of potential RNA precursors, focusing on methods for stereoselective CÀC bond construction by aldolisation and related processes. This chemistry is presented in the context of a broader picture of the potential constitutional self-assembly of RNA. Finally, the relative accessibility of RNA and alternative nucleic acids is considered. Introduction. – A robust, prebiotically plausible synthesis of RNA, if achieved, will dramatically strengthen the case for the RNA world hypothesis [1][2]. Despite nearly half a century of effort, however, the prospects for such a synthesis have appeared somewhat remote. Difficulties in the generation and oligomerisation of activated nucleotides have led to suggestions that RNA might have been preceded by a simpler informational macromolecule [1–3]. It has been suggested that a biology based on this simpler nucleic acid might have then invented RNA. According to this scheme, functional superiority of RNA would have subsequently driven the transition to a biology based on RNA, and the RNA world would have been born (Fig.